Angiotensin II for Septic Shock Treatment

January 14, 2019 updated by: Ahmed Hasanin, Cairo University

Angiotensin II for Septic Shock Treatment: Effects On Macro- and Microcirculation A Randomized, Controlled Pilot Trial (ANGSTROM Trial)

This study aims to investigate the effect of angiotensin II on microcirculation and peripheral perfusion in patients with septic shock.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Suspended

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Shock is a syndrome characterized by acute circulatory failure resulting in impaired peripheral tissue perfusion. Distributive shock is the most common type of shock and is usually caused by severe sepsis. Distributive shock is characterized by profound vasodilatation leading to decreased arterial blood pressure and impaired organ perfusion despite high cardiac output.

The use of vasopressors is an essential management line for distributive sock. Two groups of vasopressors are usually used for management of shock: catecholamines and vasopressin-like peptides. There is a continuous need for other vasopressors because:

1- Available vasopressors have narrow therapeutic window. 2- Patients with severe hypotension refractory to the currently available classes usually die.

A third system is usually engaged in the physiology of shock which is Renin-Angiotensin-aldosterone system. Angiotensin II is a natural hormone which is a potent vasopressor; moreover, angiotensin II stimulates the production of both antidiuretic hormone and adrenocorticotropin hormone.

In a pilot study, angiotensin II was reported as an effective rescue vasopressor in septic shock patients on multiple vasopressors. Angiotensin II improved mean arterial pressure and helped in reduction of the doses of catecholamines. In a recent large randomized controlled trial, angiotensin II improved blood pressure in catecholamine-resistant distributive shock patients.

Microcirculation is the primary site of oxygen and nutrient exchange. Maintenance of microcirculatory perfusion is a prerequisite for preservation of organ function. Multiple organ failure is common in patients with distributive shock despite maintenance of parameters of global perfusion due to disrupted microcirculatory perfusion. Furthermore, restoration of microcirculatory perfusion was correlated with improvement in survival. This study aims to investigate the effect of angiotensin II on peripheral microcirculation in patients with septic shock.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Egypt
      • Cairo, Egypt
        • Cairo University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 61 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Septic shock patients.
  • Aged above 18 years.
  • With cardiac index > 2.4 L/min/BSA 1.73 m2.
  • On high dose vasopressors (defined as norepinephrine infusion above 0.1 mcg/Kg/min)

Exclusion Criteria:

  • Acute coronary syndrome.
  • Impaired cardiac contractility
  • Bronchospasm.
  • Major burns
  • Liver failure.
  • Active bleeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Angiotensin group
Patients will receive Angiotensin II at a starting dose of 20 ng/Kg/min. During the first 30 minutes after randomization, the angiotensin II infusion will be titrated to achieve a mean arterial pressure of 65-75 mmHg while the norepinephrine infusion will be withdrawn and stopped. Following a stabilization of 60 minutes, the angiotensin II infusion is titrated to achieve a mean arterial pressure of 85-95 mmHg. Following a 30 minutes wash-in period and a 60 minutes stabilization period, a third set of measurements will be taken. Then, the angiotensin II infusion will be withdrawn in small steps and replaced by a norepinephrine infusion which will then be titrated to achieve a mean arterial pressure of 65-75 mmHg. Then, the final set of measurements will be taken.
Drug: Angiotensin II
Patients will receive angiotensin-II at a starting dose of 20 ng/Kg/min.
Drug: Norepinephrine
patients will receive norepinephrine infusion adjusted according to blood pressure
Other Names:
  • Noradrenaline
Placebo Comparator: Normal saline group
Patients will receive normal saline infusion in addition to norepinephrine infusion. The same mean arterial pressure levels (65-75 mmHg > 85-95 mmHg > 65-75 mmHg) will be achieved by titration of the norepinephrine infusion. Identical wash-in and stabilization periods will be kept as in the study group. Measurements will be taken at the same time points as in the study group. The maximum dose of norepinephrine applied will be 0.7 mcg/kg/min.
Drug: Norepinephrine
patients will receive norepinephrine infusion adjusted according to blood pressure
Other Names:
  • Noradrenaline
Drug: Normal saline
Patients will receive normal saline.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Mean flow index
Time Frame: 6 Hours

Mean flow index measured by Side stream dark field imaging optical probe (Microscan; MicroVision Medical, Amsterdam, Netherlands). Briefly, after gentle cleansing of the tongue by isotonic-saline-drenched gauze, avoiding pressure artifacts, 5 steady images of at least 20 seconds each will be obtained and stored under a random number. Offline blind analysis of each video will be done using a dedicated software (Automated Vascular Analysis 3.0; Academic Medical Center, University of Amsterdam, The Netherlands).

The microvascular flow index (MFI) will be used to quantify microvascular blood flow. In this score, flow is characterized as absent (0), intermittent (1), sluggish (2), or normal (3), for each patient the values from 5 videos will be averaged. Since our investigation will be focused on small vessels, calculations will be separately performed for vessels with a diameter less than 20 ųm.
6 Hours

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Proportion of perfused vessels
Time Frame: 6 Hours
Proportion of perfused vessels measured by Side stream dark field imaging optical probe (Microscan; MicroVision Medical, Amsterdam, Netherlands). Briefly, after gentle cleansing of the tongue by isotonic-saline-drenched gauze, avoiding pressure artifacts, 5 steady images of at least 20 seconds each will be obtained and stored under a random number. Offline blind analysis of each video will be done using a dedicated software (Automated Vascular Analysis 3.0; Academic Medical Center, University of Amsterdam, The Netherlands)
6 Hours
Perfused vessel density
Time Frame: 6 Hours
Perfused vessel density measured by Side stream dark field imaging optical probe (Microscan; MicroVision Medical, Amsterdam, Netherlands). Briefly, after gentle cleansing of the tongue by isotonic-saline-drenched gauze, avoiding pressure artifacts, 5 steady images of at least 20 seconds each will be obtained and stored under a random number. Offline blind analysis of each video will be done using a dedicated software (Automated Vascular Analysis 3.0; Academic Medical Center, University of Amsterdam, The Netherlands)
6 Hours
systolic blood pressure
Time Frame: 6 hours
systolic blood pressure measured in mmHg
6 hours
Diastolic blood pressure
Time Frame: 6 hours
diastolic blood pressure measured in mmHg
6 hours
Heart rate
Time Frame: 6 hours
heart rate in beats per minute
6 hours
Serum lactate
Time Frame: 6 hours
Serum lactate measured in milligrams per deciliter
6 hours
Urine output
Time Frame: 6 hours
quantity of urine in milliliters
6 hours
Serum Creatinine
Time Frame: 24 hours
serum creatinine measured in milligrams per deciliter
24 hours
Serum Sodium
Time Frame: 24 hours
Serum sodium measured in milligrams per deciliter
24 hours
Serum potassium
Time Frame: 24 hours
Serum potassium measured in milligrams per deciliter
24 hours
Cardiac output
Time Frame: 6 hours
quantity of blood pumper by the heart measured by electrical cardiometry in liters per minute
6 hours
systemic vascular resistance
Time Frame: 6 hours
systemic vascular resistance measured by electrical cardiometry
6 hours
Norepinephrine requirements
Time Frame: 6 hours
total requirement of norepinephrine needed to maintain mean arterial blood pressure above 65 mmHg
6 hours
perfusion index
Time Frame: 6 hours
proportion of pulsatile to non-pulsatile portions in peripheral circulation
6 hours
total fluid intake
Time Frame: 24 hours
amount of fluids received by the patient in milliliters
24 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Cairo University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Martin W Dünser, Professor, Department of critical care, University of London college hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2019

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2019

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 15, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 1, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 1, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 5, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 16, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 14, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • N-68-2017

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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